X-101231741-C-A

Variant names:

• chrX-101231741-C-A
• rs781126747
• NM_001939.3:c.94C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001939.3(DRP2):​c.94C>A​(p.Arg32Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,096,771 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: DRP2 NM_001939.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 0 publications found

Genes affected

DRP2 (HGNC:3032): (dystrophin related protein 2) Members of the dystrophin family of proteins perform a critical role in the maintenance of membrane-associated complexes at points of intercellular contact in vertebrate cells. The protein encoded by this gene is predicted to resemble certain short C-terminal isoforms of dystrophin and dystrophin-related protein 1 (DRP1 or utrophin). DRP2 is expressed principally in the brain and spinal cord. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

DRP2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=0.717 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001939.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRP2	NM_001939.3	MANE Select	c.94C>A	p.Arg32Arg	synonymous	Exon 3 of 24	NP_001930.2	Q13474-1
	DRP2	NM_001171184.2		c.-117-4119C>A		intron	N/A	NP_001164655.1	Q13474-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRP2	ENST00000395209.8	TSL:1 MANE Select	c.94C>A	p.Arg32Arg	synonymous	Exon 3 of 24	ENSP00000378635.3	Q13474-1
	DRP2	ENST00000402866.5	TSL:5	c.94C>A	p.Arg32Arg	synonymous	Exon 3 of 24	ENSP00000385038.1	Q13474-1
	DRP2	ENST00000538510.1	TSL:2	c.94C>A	p.Arg32Arg	synonymous	Exon 1 of 22	ENSP00000441051.1	Q13474-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182302 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1096771 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362151

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.00 AC: 0 AN: 35157

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30185

South Asian (SAS) AF: 0.0000556 AC: 3 AN: 53997

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841029

Other (OTH) AF: 0.00 AC: 0 AN: 46041

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	8.8
DANN	Benign	0.68
PhyloP100		0.72
PromoterAI		-0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781126747; hg19: chrX-100486730;